Biomedical subjects
Robert Campbell
Publications and source records attributed to Robert Campbell.
Criteria for chemical selection for programs on human milk surveillance and research for environmental chemicals.
The people of the United States is exposed to a large number of chemicals in their daily lives. In order to prioritize chemicals that should be considered for surveillance of and/or research in human milk, criteria were developed at the Technical Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States. The criteria include (1) lipid solubility and/or persistence in the environment; (2) extensive exposure (e.g., high-production-volume chemicals and chemicals in personal care products); (3) known or suspected toxicity in a biological system; (4) historical interest, trend information; (5) chemicals of emerging concern; and (6) chemicals for medicinal use and chemicals in occupational settings. A working list of chemicals was developed for each of the criteria. It should be noted that more than one criterion may be applicable to a selected chemical, but the selected chemical should possess at least one of these designated criteria. It is hoped that by following a cohort of nursing women through their lactational cycle for a group of these chemicals, data generated will indicate the extent of infant exposure and may suggest methods for risk management to decrease inadvertent exposure for breast-feeding mothers and infants. While not the focus of this article, certain endogenous chemicals in human milk beneficial to the health of the infant warrant study as well.
Conclusions, research needs, and recommendations of the expert panel: technical workshop on human milk surveillance and research for environmental chemicals in the United States.
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Copepod hatching success in marine ecosystems with high diatom concentrations.
Diatoms dominate spring bloom phytoplankton assemblages in temperate waters and coastal upwelling regions of the global ocean. Copepods usually dominate the zooplankton in these regions and are the prey of many larval fish species. Recent laboratory studies suggest that diatoms may have a deleterious effect on the success of copepod egg hatching. These findings challenge the classical view of marine food-web energy flow from diatoms to fish by means of copepods. Egg mortality is an important factor in copepod population dynamics, thus, if diatoms have a deleterious in situ effect, paradoxically, high diatom abundance could limit secondary production. Therefore, the current understanding of energy transfer from primary production to fisheries in some of the most productive and economically important marine ecosystems may be seriously flawed. Here we present in situ estimates of copepod egg hatching success from twelve globally distributed areas, where diatoms dominate the phytoplankton assemblage. We did not observe a negative relationship between copepod egg hatching success and either diatom biomass or dominance in the microplankton in any of these regions. The classical model for diatom-dominated system remains valid.
N-Cycloalkanoyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.
A systematic structure-activity relationship investigation of the lead compound 1 resulted the identification of several N-[(substituted alkyl)cycloalkanoyl]-4-[((2,6-dichlorophenyl)carbonyl)amino]-L-phenylalanine derivatives as potent VCAM/VLA-4 antagonists. The data are consistent with a model of these compounds in which these alkanoylphenylalanines reside in a compact gauche (-) bioactive conformation.
N-Aroyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.
A series of N-benzoyl-4-[(2,6-dichlorobenzoyl)amino]-L-phenylalanine derivatives was prepared in order to optimize the substitution on the N-benzoyl moiety for VCAM/VLA-4 antagonist activity. Disubstitution in the 2- and 6-positions is favored and a range of small alkyl and halogen are tolerated. A model of the bioactive conformation of these compounds is proposed.
Focused library approach for identification of new N-acylphenylalanines as VCAM/VLA-4 antagonists.
A structure-based focused library approach was employed in an effort to identify more lipophilic replacements for the N-benzylpyroglutamyl group of the VCAM/VLA-4 antagonist 2. This effort led to the discovery of two new classes of potent antagonists characterized by the N-(alpha-phenylcyclopentanoyl- and the N-(2,6-dimethylbenzoyl)-derivatives 60 and 64.
N-acyl-L-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation.
A series of N-benzylpyroglutamyl-L-phenylalanine derivatives bearing carbamoyl substituents in the 3- or 4-positions was prepared and assayed for inhibition of the interaction between VCAM and VLA-4. Potent inhibition was observed in a number of analogues with substitution in the 4-position favored over the 3-position. A crystal structure of the key intermediate 25 indicates that it accesses a low energy conformation which closely matches key pharmacophores of a structurally characterized cyclic peptide.
Heel pad thickness--a contributing factor associated with plantar heel pain in young adults.
Thirty-three runners were clinically diagnosed with plantar heel pain (PHP) and 107 runners were designated into a non-PHP group (NPHP). Cases were matched with a further control group of 64 subjects with regard to body mass index and age. A weight-bearing platform measured heel pad thickness by real-time ultrasound scanning. The results demonstrated a significant difference between the PHP and both the NPHP and control groups (P <0.05). The results also demonstrated that body mass index had a significant effect (P <0.05) on the heel pad thickness of all subjects, regardless of the heel pad group. The results from the current study, with some precaution, conclude that body mass index as such is not related to PHP in the athletic population. In the current study the observed differences of body mass index on heel pad thickness between the PHP and NPHP groups, and the similarity between the control group and NPHP subjects suggests other risk factors may play an important role in heel pad thickening and associated development of PHP.
Oxazole- and imidazole-based Ser-Leu dipeptide mimetics in potent inhibitors of antigen presentation by MHC class II DR molecules.
Imidazole and oxazole derivatives 1 to 4 were designed and prepared as dipeptide mimetics to replace the Ser-Leu dipeptide sequence of Ro-25-9980 (Ac-(Cha)-RAMA-S-L-NH2), a peptidic inhibitor of antigen binding to major histocompatibility complex (MHC) class II DR molecules linked to rheumatoid arthritis (RA). The most potent analog in binding assays (IC50 = 30 nM in DRB1*0401 binding; 1.6 times as potent as Ro 25-9980) was 16, Ac-(Cha)RAMA-(S)S-psi(oxazole)-L-NH2. The SAR of peptide hybrids 10 to 24, prepared by incorporating the dipeptide mimetics 1 to 4 is discussed. Of these hybrids, 23 and 24, analogs that incorporated the imidazole and oxazole mimetics as well as optimized variants at positions 3 to 5, were found to have 70 to 80 nM binding affinity comparable to the parent peptide in DRB 1*0401 binding and were also active in DRB1*0101 binding, while being resistant to proteolysis by cathepsin B. Both of these compounds showed inhibitory activity in an antigen-stimulated T-cell proliferation assay, indicating their potential to suppress autoimmune responses and as leads for therapeutic agents to treat RA.
Reliability of weight-bearing heel pad thickness measurements by ultrasound.
OBJECTIVE: To evaluate the intra- and inter-operator reliability of measuring weightbearing heel pad thickness in healthy subjects. BACKGROUND: Heel pad thickness has been reported to be an important factor in determining stresses observed in healthy as well as pathological feet. To date no published data are available on inter- and intra-operator variation in sonographic heel pad thickness measurements in adults. METHOD: bilateral heel pad thickness was measured in 10 adult subjects, with no history of plantar heel pain, by two experienced operators, on two separate occasions. Limits of agreement for three replicate measurements by each ultrasonographer and for replicate measurements were determined. RESULTS: Replicate heel pad thickness measurements in 95% of cases differ by less than 0.39 mm, and the magnitude of variations is similar when measurements are made by either single or different ultrasonographers, and were similar for right and left heel pad thickness measurements. Between scan measurements demonstrated a coefficient of variation of 3.2%. CONCLUSION: Weightbearing heel pad thickness measurements by ultrasound using a standardised technique in normal adult feet are reasonably reliable. RELEVANCE: Heel pad thickness can be measured reliably. Heel pad thickness may be an important predictor in the cause of ulceration in diabetics, and a potential risk factor in plantar pain affecting athletes. Further work assessing the heel pad in pathological conditions and athletes merits further study.
Radiofrequency thermoneurolysis of peripheral nerves for control of trigeminal neuralgia.
Radiofrequency thermoneurolysis (RFTN) was performed in the peripheral infraorbital and inferior alveolar nerves of eight patients with paroxysmal trigeminal neuralgias. Pain severity as measured by tourniquet test and global estimate was significantly reduced in seven of eight patients. The sharp, paroxysmal component of neuralgia was controlled in all seven successes although significant pain was recurring in two patients one year post-operatively. Neurosensory threshold responses to tactile-discriminative stimuli were not permanently changed from pre-lesion levels but pain detection and pain tolerance threshold responses to mechanical pin-pressure and thermal stimuli were significantly raised, suggesting that RFTN is more selective for small myelinated and unmyelinated fibers. This procedure was found to be safe, effective, simple, and predictable on the basis of diagnostic blocks. Results suggest that it is a temporary control measure which nevertheless can be repeated. It may also prove useful as a test to identify those patients who may experience anesthesia dolorosa. It is suggested for patients with toxic responses to medical therapy and as an alternative to more invasive surgeries for the long-term management of trigeminal neuralgia.
Sun protection of children at the beach.
BACKGROUND: We wanted to determine the frequency with which sun protection measures are used by children at the beach. METHODS: A cross-sectional study was undertaken that combined a brief, structured interview with direct observation of the sun protection methods (sunscreen, clothing, hats, shade) used for children at a public beach in Florida. RESULTS: Of the 139 children observed, 97 (69.8%) had some form of sun protection used on all three body regions (head, torso, legs), while only 8 (5.8%) had none of the three body regions protected. Sunscreen was the most common method of sun protection (84.9%), and other methods were less frequently used (shirt 11.5%, pants 26.6%, hat 8.6%, shade 14.4%). Sun protection use differed by sex, with girls having better protection of their head and torso, and boys slightly better protection of their legs. CONCLUSIONS: Using direct observation, we found that parents frequently use sun protection measures (mainly sunscreen) for their children while at the beach. Parents primarily rely on the use of sunscreen, rather than such measures as avoiding the sun, using shade, or protective clothing.